Inclusion Criteria:
- Have documentation of a clinical genetic test demonstrating the presence of a confirmed repeat expansion in the C9orf72 gene from a CLIA certified laboratory - Score ≥ 18 on the Mini-Mental State Exam (MMSE) at Screening - Have a reliable caregiver to accompany the patient to all study visits.
- For patients with ALS (with or without FTD):
- Diagnosis of ALS (probable, possible, laboratory-supported probable or definite) according to the World Federation of Neurology revised E1 Escorial criteria - Onset of weakness within 3 years prior to Screening - Slow vital capacity (SVC) ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position) - ALS Functional Rating Scale-Revised (ALSFRS-R) ≥ 30 at Screening - For patients with FTD:
- A gradual, progressive decline in behavior, language, or motor function consistent with C9ORF72 hexanucleotide expansion-related syndrome such as behavioral variant FTD, primary progressive vaphasia, or amnestic syndrome - CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD) global score of 0.5-2.0 at Screening Exclusion Criteria:
- Presence of other significant neurological or psychiatric disorders - History of significant brain abnormality, including, but not limited to, prior hemorrhage or infarct, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma); symptoms or signs of elevated intracranial pressure, e.g., symptoms or history of head injury or abnormal funduscopic exam. If there is history or evidence on neurologic exam suggesting possible subdural hematoma (SDH), patients should be fully evaluated, including magnetic resonance imaging (MRI) if indicated, to exclude significant, new SDH

This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 2-arm study with a long-term, open-label treatment phase in patients with C9ORF72 ALS and/or FTD. This study includes a 6-week Screening Period, a 24-week Double-blind Treatment Period, a 24-week Open-label Treatment Period, and a Follow-up Visit 4 weeks post-treatment.

• Transposon Therapeutics, Inc.

NCT04993755 (First Published: 7/19/2021)